Defective carnitine metabolism may play role in autism

HOUSTON — (May 7, 2012) – The deletion of part of a gene that plays a role in the synthesis of carnitine – an amino acid derivative that helps the body use fat for energy – may play a role in milder forms of autism, said a group of researchers led by those at Baylor College of Medicine (http://www.bcm.edu) and Texas Children’s Hospital (http://www.texaschildrens.org).

Beaudet and his international group of collaborators believe the gene deletion leads to an imbalance in carnitine in the body. Meat eaters receive about 75 percent of their carnitine from their diet. However, dietary carnitine levels are low in vegetarians and particularly in vegans. In most people, levels of carnitine are balanced by the body’s ability to manufacture its own carnitine in the liver, kidney and brain, starting with a modified form of the amino acid lysine.

Carnitine deficiency has been identified when not enough is absorbed through the diet or because of medical treatments such as kidney dialysis. Genetic forms of carnitine deficiency also exist, which are caused when too much carnitine is excreted through the kidneys.

In this new inborn error, there is a deletion in the second exon – the protein-coding portion of a gene – of the TMLHE gene, which includes the genetic code for the first enzyme in the synthesis of carnitine (TMLHE stands for trimethyllysine epsilon which encodes the enzyme trimethyllysine dioxygenase).

Studies in the laboratory that identified the deletion were led by Dr. Patricia B.S. Celestino-Soper, as a graduate student in Beaudet’s laboratory at BCM and by Dr. Sara Violante, a graduate student in the laboratory of Dr. Frédéric M. Vaz of the Academic Medical Center in Amsterdam.

To determine the frequency of the gene deletion, Beaudet and his colleagues tested male autism patients who were the only people with the disorder in their families (simplex families) from the Simons Simplex Collection, the South Carolina Early Autism Project and Houston families. In collaboration with laboratories and researchers in Nashville, Los Angeles, Paris, New York, Toronto and Cambridge (United Kingdom), they tested affected male siblings in families with more than one male case of autism (multiplex families).

When they looked at the TMLHE genes in males affected by autism and compared them to normal controls, they found that the gene alteration is a fairly common one, occurring in as many as one in 366 males unaffected by autism. It was not significantly more common in males within families in which there is only one person with autism. However, it is nearly three times more common in families with two or more boys with autism.

Beaudet said most of the affected males with the deletion did not have syndromic autism that is frequently associated with other serious diseases. In many instances, syndromic autism affects physical development as well as cognitive, which is reflected in their facial features as well as other parts of their bodies. None of the six boys affected with autism (where information was available) had the syndromic form of disease. Their intelligence quotients and cognitive scores varied, with some being far below normal and others normal.

“Most of the males we identified with the TMLHE deficiency were apparently normal as adults,” said Beaudet, although detailed information on learning and behavior was not available on these “control” males. “The gene deletion is neither necessary nor sufficient in itself to cause autism.”

“TMLHE deficiency itself is likely to be a weak risk factor for autism, but we need to do more studies to replicate our results,” Beaudet said. He estimated that at the rates found in his study, the deficiency might be a factor in about 170 males born with autism per year in the United States. This would equate to about one-half of one percent of autism cases.

The authors from Amsterdam found major increases in some carnitine-related chemicals and absence of others in both urine and plasma. These metabolic alterations were found to be predictive of the dysfunction of the TMLHE gene and therefore can be used to identify males with this disorder

It remains uncertain whether TMLHE deficiency is benign or causes autism by affecting the function of neurons through toxic accumulation or deficiency of a variety of chemical metabolites.

“We believe that the most attractive hypothesis at this time is that the increased risk of autism is modified by dietary intake of carnitine from birth through the first few years of life,” said Beaudet.

He and his colleagues are undertaking three studies to further their understanding of the TMLHE deficiency. In one, they will attempt to replicate the findings in multiplex families. In a second, they will study carnitine levels in the cerebrospinal fluid of infants with autism – both those who have the gene deficiency and those who do not. In a third study, they plan to begin giving boys under age 5 with autism carnitine or a related supplement and determine whether this improves the behavior of those with the TMLHE deficiency and those without.

Researchers see BPA effects in monkey mammary glands

Study adds to growing health concerns about common plastic additive

PULLMAN, Wash.—A new study finds that fetal exposure to the plastic additive bisphenol A, or BPA, alters mammary gland development in primates. The finding adds to the evidence that the chemical can be causing health problems in humans and bolsters concerns about it contributing to breast cancer.

“Previous studies in mice have demonstrated that low doses of BPA alter the developing mammary gland and that these subtle changes increase the risk of cancer in the adult,” says Patricia Hunt, a geneticist in Washington State University’s School of Molecular Biosciences. “Some have questioned the relevance of these findings in mice to humans. But finding the same thing in a primate model really hits uncomfortably close to home.”

The research appears in the latest Proceedings of the National Academies of Sciences. Hunt and Tufts University School of Medicine researchers Ana Soto and Carlos Sonnenschein—all pioneers in the effects of BPA—co-designed the study with Catherine VandeVoort at the University of California at Davis, where the study was performed.

The Tufts researchers compared the structure of newborn mammary glands from BPA-exposed and unexposed female rhesus macaques. Pregnant monkeys were fed a piece of fruit containing a small amount of BPA each day during the gestational period corresponding to the human third trimester of pregnancy, resulting in blood levels of BPA comparable to those of many Americans today.

The researchers found that, at birth, the density of mammary buds was significantly increased in BPA-exposed monkeys, and the overall development of the mammary gland was more advanced compared to unexposed monkeys. Previous studies in the Soto and Sonnenschein laboratories have shown that exposing rodents to tiny amounts of BPA can alter mammary gland development, leading to pre-cancerous and cancerous lesions when the animals exposed in utero reach adult age.

The researchers say the primate research makes them confident that the rodent mammary gland is a reliable model to study developmental exposures to chemicals like BPA that disrupt a mammal’s estrogen activity.

“This study buttresses previous findings showing that fetal exposure to low xenoestrogen levels causes developmental alterations that in turn increase the risk of mammary cancer later in life,” says Soto. “Because BPA is chemically related to diethylstilbestrol, an estrogen that increased the risk of breast cancer in both rodents and women exposed in the womb, the sum of all these findings strongly suggests that BPA is a breast carcinogen in humans and human exposure to BPA should be curtailed.”

Gut flora affects maturation of B cells in infants

IMAGE:This is Anna-Carin Lundell of the Institute of Medicine, Sahlgrenska Academy, University of Gothenburg.

Infants whose gut is colonised by E. coli bacteria early in life have a higher number of memory B cells in their blood, reveals a study of infants carried out at the Sahlgrenska Academy at the University of Gothenburg, Sweden.

The bacteria in our gut outnumber the cells in our bodies by a factor of ten and are extremely important for our health because they stimulate the maturation of the immune system. The normal bacterial flora in the gut is established at the very beginning of our lives, but an increasingly hygienic lifestyle has led to changes in this flora.

Colonised ever later

These days Swedish children are colonised by E. coli bacteria later and later. They also have a less varied bacterial flora and a smaller turnover of bacterial strains in the gut than children in developing countries. Meanwhile, diseases caused by deficiencies in immune regulation have increased sharply, making allergies a major public health issue in the Western World.

B cells play key role in development of allergies

Researchers at the University of Gothenburg’s Sahlgrenska Academy have looked at B cells, a type of white blood cell that produces antibodies that can protect the body against infection and play a key role in the development of allergies. By studying 65 healthy newborn babies in the Västra Götaland region, researcher Anna-Carin Lundell and her colleagues were able to show that infants whose gut is colonised by E. coli bacteria during the first few weeks of life had a higher number of memory B cells at the age of both four and 18 months.

“The results are important for understanding the relationship between our complex bacterial gut flora and our immune system, and show what we risk losing with an excessively hygienic lifestyle,” Anna-Carin Lundell explains.

“Most of the bacteria around us are harmless, and we should see them as a very important form of training so that our children’s immune systems mature properly. Healthy newborns should not be over-protected against natural exposure of the gut flora.”

Flavonoid compound found in foods and supplements shown to prevent the formation of blood clots

Research findings offer a new direction for a therapeutic agent to prevent stroke, heart attack

BOSTON — A compound called rutin, commonly found in fruits and vegetables and sold over the counter as a dietary supplement, has been shown to inhibit the formation of blood clots in an animal model of thrombosis.

These new findings, led by investigators at Beth Israel Deaconess Medical Center (BIDMC) and published in today’s on-line issue of The Journal of Clinical Investigation (JCI), identify a novel strategy for preventing thrombosis, and help pave the way for clinical testing of this popular flavonoid as a therapy for the prevention and treatment of stroke and heart attack, as well as deep venous thrombosis (DVT) and pulmonary embolism.

“It’s not always fully appreciated that the majority of Americans will die as the result of a blood clot in either their heart or their brain,” says senior author Robert Flaumenhaft, MD, PhD, an investigator in the Division of Hemostasis andThrombosis at BIDMC and Associate Professor of Medicine at Harvard Medical School. “Approximately half of all morbidity and mortality in the United States can be attributed to heart attack or stroke.”

The study focused on protein disulfide isomerase (PDI) which is found in all cells. Investigators in BIDMC’s Division of Hemostasis and Thrombosis had previously shown that PDI is rapidly secreted from both platelets and endothelial cells during thrombosis, when a clot forms in a blood vessel, and that inhibition of PDI could block thrombosis in a mouse model.

“This was a transformative and unanticipated finding because it identified, for the first time, that PDI is secreted from cells in a live animal and is a potential target for preventing thrombosis,” says Flaumenhaft. However, because intracellular PDI is necessary for the proper synthesis of proteins, the scientists had to identify a specific compound that could block the thrombosis-causing extracellular PDI – without inhibiting the intracellular PDI.

They began by conducting a high-throughput screen of a wide array of compounds to identify PDI inhibitors. Among the more than 5,000 compounds that were screened, quercetin-3-rutinoside (rutin) emerged as the most potent agent. “Rutin was essentially the champion compound,” says Flaumenhaft.

A bioflavonoid that is naturally found in many fruits, vegetables and teas including onions, apples and citrus fruits, rutin is also sold as an herbal supplement, having received a special designation for safety from the U.S. Food and Drug Administration (FDA). Surprisingly, studies of the rutin molecule demonstrated that the same part of the molecule that provides rutin with its ability to inhibit PDI also prevents the compound from entering cells. “That finding explained how this compound can be both a potent inhibitor of PDI and a safe food supplement,” says Flaumenhaft. “Our next questions were, ‘Is this compound anti-thrombotic? Can it prevent blood clots?'”

The team went on to test rutin in a mouse model of thrombosis. Because they knew that humans would be taking rutin in pill form, they included studies in which the compound was administered orally and determined that it successfully retained its anti-thrombotic properties when it was metabolized following oral ingestion.

“Rutin proved to be the most potently anti-thrombotic compound that we ever tested in this model,” says Flaumenhaft. Of particular note, rutin was shown to inhibit both platelet accumulation and fibrin generation during thrombus formation. “Clots occur in both arteries and in veins,” explains Flaumenhaft. “Clots in arteries are platelet-rich, while those in veins are fibrin-rich. This discovery suggests that a single agent can treat and prevent both types of clots.”

Even with the use of existing anti-clotting therapies, such as aspirin, clopidogrel (Plavix) and warfarin (Coumadin), each year there are approximately 400,000 recurrent episodes among patients who previously experienced a stroke or heart attack, says Flaumenhaft.

“A safe and inexpensive drug that could reduce recurrent clots could help save thousands of lives,” he adds. “These pre-clinical trials provide proof-of-principle that PDI is an important therapeutic target for anti-thrombotic therapy, and because the FDA has already established that rutin is safe, we are poised to expeditiously test this idea in a clinical trial, without the time and expense required to establish the safety of a new drug.”

Consumption of probiotics associated with reduced risk of diarrhea from antibiotic use

Consumption of probiotics (live microorganisms, which may occur naturally in foods such as yogurt, intended to confer a health benefit when consumed) is associated with a reduced risk of antibiotic-associated diarrhea, a common adverse effect of antibiotic use, according to a review and meta-analysis of previous studies published in the May 9 issue of JAMA.

“The use of antibiotics that disturb the gastrointestinal flora [microbes] is associated with clinical symptoms such as diarrhea, which occurs in as many as 30 percent of patients. Symptoms range from mild and self-limiting to severe, particularly in Clostridium difficile infections, and antibiotic-associated diarrhea (AAD) is an important reason for nonadherence with antibiotic treatment,” according to background information in the article. Potentially, probiotics maintain or restore gut microecology (microbial ecology) during or after antibiotic treatment. “There is an increasing interest in probiotic interventions, and evidence for the effectiveness of probiotics in preventing or treating AAD is also increasing,” the authors write.

The majority of the RCTs used Lactobacillus-based interventions alone or in combination with other genera (a subdivision of a family of organisms); strains were poorly documented. Of all included trials, 63 reported the number of participants with diarrhea and the number of participants randomized to both treatment groups. Across 63 RCTs (n = 11,811 participants), probiotic use was associated with a 42 percent lower risk of developing diarrhea compared with a control group not using probiotics. The result was consistent across a number of subgroup and sensitivity analyses. The treatment effect equates to a number needed to treat of 13.

The researchers note that there exists significant heterogeneity (differences across studies) in pooled results and the evidence is insufficient to determine whether this association varies systematically by population, antibiotic characteristic, or probiotic preparation.

“In summary, our review found sufficient evidence to conclude that adjunct probiotic administration is associated with a reduced risk of AAD. This generalized conclusion likely obscures heterogeneity in effectiveness among the patients, the antibiotics, and the probiotic strains or blends. Future studies should assess these factors and explicitly assess the possibility of adverse events to better refine our understanding of the use of probiotics to prevent AAD,” the authors conclude.

Psychiatric medication effects on brain structure

Biological Psychiatry article provides insights from animal studies

Philadelphia, PA, May 8, 2012 – It is increasingly recognized that chronic psychotropic drug treatment may lead to structural remodeling of the brain. Indeed, clinical studies in humans present an intriguing picture: antipsychotics, used for the treatment of schizophrenia and psychosis, may contribute to cortical gray matter loss in patients, whereas lithium, used for the treatment of bipolar disorder and mania, may preserve gray matter in patients.

However, the clinical significance of these structural changes is not yet clear. There are many challenges in executing longitudinal, controlled, and randomized studies to evaluate this issue in humans, particularly because there are also many confounding factors, including illness severity, illness duration, and other medications, when studying patients.

It is therefore critical to develop animal models to inform the clinical research. To accomplish this, a group of researchers at King’s College London, led by Dr. Shitij Kapur, developed a rat model using clinically relevant drug exposure and matched clinical dosing in combination with longitudinal magnetic resonance imaging. They administered either lithium or haloperidol (a common antipsychotic) to rats in doses equivalent to those received by humans. The rats received this treatment daily for eight weeks, equivalent to 5 human years, and underwent brain scans both before and after treatment.

Dr. Kapur explained their findings, “Using this approach, we observed that chronic treatment with haloperidol leads to decreases in cortical gray matter, whilst lithium induced an increase, effects that were reversible after drug withdrawal.” Gray matter was decreased by 6% after haloperidol treatment, but increased by 3% after lithium treatment.

“These important observations clarify conflicting findings from clinical trials by removing many of the confounding effects,” commented Dr. John Krystal, Editor of Biological Psychiatry. “Whether these changes in brain structure underlie the benefits or side effects of these medications remain to be seen. However, they point to brain effects of established medications that are not well understood, but which may hold clues to new treatment approaches.”

“Whilst these intriguing findings are consistent with available clinical data, it should be noted these studies were done in normal rats, which do not capture the innate pathology of either schizophrenia or bipolar disorder,” Kapur added. “Moreover, because the mechanism(s) of these drug effects remain unknown, further studies are required, and one should be cautious in drawing clinical inferences. Nevertheless, our study demonstrates a new and powerful model system for further investigation of the effects of psychotropic drug treatment on brain morphology.”

College men find steroids for better game less ethical than stimulants for better grades, study says

Misuse of prescription drugs seen as ‘more necessary’ for success, study finds

WASHINGTON – In the eyes of young college men, it’s more unethical to use steroids to get an edge in sports than it is to use prescription stimulants to enhance one’s grades, according to new research published by the American Psychological Association.

And students who had themselves used stimulants without a prescription were more inclined to see such drug use as acceptable, according to the findings, which were published online in the APA journal Psychology of Addictive Behaviors. This is one of the first studies to compare perceptions of off-label prescription drug use with perceptions of steroids performance enhancers.

“This is consistent with the idea that using performance enhancers is viewed as less ethical in the sporting world than in the academic world,” said the study’s lead author, Tonya Dodge, PhD, of George Washington University. “Interestingly, the students in our study considered off-label prescription drug use as more effective for success than using steroids.”

Approximately 1,200 college freshmen (73 percent white) at Pennsylvania State University answered a questionnaire that presented two scenarios. One described “Bill,” a sprinter for his college track team who does not have a lot of time to train before the championship meet and is worried he won’t be able to improve. He gets steroids from a friend and ends up performing better than expected and wins the championship race.

The second scenario presents “Jeff,” a college student facing midterm exams who is worried that his grades in class may be low. He doesn’t have much time to study so he gets some Adderall, a prescription stimulant, from a friend who tells him it will help him focus at exam time. Jeff takes the pills and ends up getting better midterm grades than he expected.

After reading both scenarios, the students were asked how strongly they agreed or disagreed with four statements: “Bill/Jeff is a cheater for using steroids/Adderall,” and, “Taking steroids/Adderall was necessary for Bill/Jeff to do well.”

The students were also asked if they had ever misused prescription stimulant drugs, such as Adderall, Ritalin or Dexedrine, or if they had ever used steroids. Less than 1 percent of the sample reported having ever used steroids while about 8 percent said they had misused prescription stimulants in the last 12 months. This compares to 8 percent to 34 percent of college students who have reported misusing prescription stimulants and 1.5 percent of adolescents and young adults who have misused anabolic steroids.

The researchers also asked the men if they had played a sport in high school to determine if that would affect their judgments.

Participants significantly rated Bill, the steroid user, as more of a cheater than Jeff, the prescription drug user. This difference got bigger if the students reported having misused prescription stimulants themselves in the past or if they had played a sport.

Overall, the students were more likely to consider Jeff’s Adderall use more necessary to succeed than Bill’s steroid use regardless of whether they had misused prescription stimulants in the past or had played a sport. “One reason students may have felt Adderall was more necessary than steroids for success is because people may believe intelligence is less malleable than athletic ability. This view of intelligence might have led the students in this study to believe that taking Adderall would increase intellectual capacity,” said Dodge. “This research can help mold future prevention efforts around off-label prescription stimulant use in the academic world.”

Ralph’s Note : Interesting because Rarely do we think of them both being the same. Does that mean we value the purity sports more than education.

BOSTON, MA—According to research from Brigham and Women’s Hospital (BWH), the ingredient that gives hot sauce its heat could play a role in the future of weight loss.

Ali Tavakkoli, MD, BWH Department of Surgery, and his team have published a study investigating whether two surgeries called vagal de-afferentation-which uses capsaicin, the component responsible for the chili pepper’s burning sensation-and vagatomy can achieve weight loss and reduce the risk of obesity-related diseases with fewer side effects when compared to today’s bariatric surgical options.

The study is published in the May issue of Digestive Diseases and Sciences. The study is accompanied by an editorial by Edward A. Fox, PhD, Purdue University.

After testing the two surgeries in the lab, the researchers found that vagotomy significantly reduced total body fat, as well as visceral abdominal fat-the “beer belly” fat that pads the spaces between abdominal organs. Vagal de-afferentation also reduced these fats, but to a lesser degree. However, according to the researchers, the reduction is still remarkable.

“The reduction in visceral fat is particularly important,” said Tavakkoli. “High visceral fat volume is a marker of obesity and obesity-related diseases, such as diabetes. Preferentially lost visceral fat after vagal de-afferentation highlights the potential for this procedure.”

Vagotomy involves removing the vagus nerve, which sends information between the gut and the brain. Vagal de-afferentation also involves the vagus nerve. But rather than removing the nerve completely, surgeons use capsaicin to destroy only certain nerve fibers.

Capsaicin destroys the nerve fibers that take signals from the gut to the brain, leaving intact the nerve fibers that send signals in the opposite direction, from the brain to the gut.

Between the two surgeries, vagal de-afferentation is associated with fewer side effects.

The researchers note that more work needs to be done on whether these surgeries can be used on humans, and whether capsaicin could be applied directly to human vagal fibers. The study results, however, provide promise of what the future can hold.

“As demand for surgeries that reduce weight and obesity-related diseases increases, procedures that can achieve success in a less invasive fashion will become increasingly important,” said Tavakkoli. “This is an important and developing surgical discipline, especially as diabetes rates soar worldwide, and people try to find effective therapies to fight this epidemic.”

This research was supported by Harvard Clinical Nutrition Center, Berkeley Fellowship and George Herbert Hunt Travelling Fellowship, and Nutricia Foundation Fellowship

First study investigating possible link between sunscreen ingredient and endometriosis

Scientists are reporting a possible link between the use of sunscreen containing a certain ingredient that mimics the effects of the female sex hormone estrogen and an increased risk of being diagnosed with endometriosis, a painful condition in which uterine tissue grows outside the uterus. They describe the report, published in ACS’ journal Environmental Science & Technology, as the first to examine whether such a connection may exist.

Kurunthachalam Kannan and colleagues explain that some sunscreens and other personal care products contain benzophenone (BP)-type ingredients that are very effective in blocking potentially harmful ultraviolet rays from the sun. Small amounts of BPs can pass through the skin and be absorbed into the blood, where they mimic the effects of estrogen. Endometriosis, which affects up to 1-in-10 women of reproductive age, needs estrogen to develop. Despite those facts, scientists until now had not checked for a connection between the use of BP sunscreens and the likelihood of being diagnosed with endometriosis.

To fill that knowledge gap, the scientists analyzed BP levels in the urine of 625 women who underwent surgery for endometriosis. They found that high levels of one BP called 2,4OH-BP were associated with an increased risk of an endometriosis diagnosis.Women tended to have higher levels of BPs during the summer months and if they lived in sunny California, further suggesting a link with sunscreens. “Our results invite the speculation that exposure to elevated 2,4OH-BP levels may be associated with endometriosis,” say the researchers.

Vitamin K2: New hope for Parkinson’s patients?

Neuroscientist Patrik Verstreken, associated with VIB and KU Leuven, succeeded in undoing the effect of one of the genetic defects that leads to Parkinson’s using vitamin K2. His discovery gives hope to Parkinson’s patients. This research was done in collaboration with colleagues from Northern Illinois University (US) and will be published this evening on the website of the authorative journal Science.

“It appears from our research that administering vitamin K2 could possibly help patients with Parkinson’s. However, more work needs to be done to understand this better,” says Patrik Verstreken.

Malfunctioning power plants are at the basis of Parkinson’s.

If we looked at cells as small factories, then mitochondria would be the power plants responsible for supplying the energy for their operation. They generate this energy by transporting electrons. In Parkinson’s patients, the activity of mitochondria and the transport of electrons have been disrupted, resulting in the mitochondria no longer producing sufficient energy for the cell. This has major consequences as the cells in certain parts of the brain will start dying off, disrupting communication between neurons. The results are the typical symptoms of Parkinson’s: lack of movement (akinesia), tremors and muscle stiffness.

The exact cause of this neurodegenerative disease is not known. In recent years, however, scientists have been able to describe several genetic defects (mutations) found in Parkinson’s patients, including the so-called PINK1 and Parkin mutations, which both lead to reduced mitochondrial activity. By studying these mutations, scientists hope to unravel the mechanisms underlying the disease process.

Paralyzed fruit flies

Fruit flies (Drosophila) are frequently used in lab experiments because of their short life spans and breeding cycles, among other things. Within two weeks of her emergence, every female is able to produce hundreds of offspring. By genetically modifying fruitflies, scientists can study the function of certain genes and proteins. Patrik Verstreken and his team used fruitflies with a genetic defect in PINK1 or Parkin that is similar to the one associated with Parkinson’s. They found that the flies with a PINK1 or Parkin mutation lost their ability to fly.

Upon closer examination, they discovered that the mitochondria in these flies were defective, just as in Parkinson’s patients. Because of this they generated less intracellular energy – energy the insects needed to fly. When the flies were given vitamin K2, the energy production in their mitochondria was restored and the insects’ ability to fly improved. The researchers were also able to determine that the energy production was restored because the vitamin K2 had improved electron transport in the mitochondria. This in turn led to improved energy production.

Conclusion

Vitamin K2 plays a role in the energy production of defective mitochondria. Because defective mitochondria are also found in Parkinson’s patients with a PINK1 or Parkin mutation, vitamin K2 potentially offers hope for a new treatment for Parkinson’s.

People with Type 2 diabetes are usually advised to keep a low-fat diet. Now, a study at Linköping University shows that food with a lot of fat and few carbohydrates could have a better effect on blood sugar levels and blood lipids.

The results of a two-year dietary study led by Hans Guldbrand, general practitioner, and Fredrik Nyström, professor of Internal Medicine, are being published in the prestigious journal Diabetologia. 61 patients were included in the study of Type 2, or adult-onset diabetes. They were randomized into two groups, where they followed either a low-carbohydrate (high fat) diet or a low-fat diet.

In both groups, the participants lost approximately 4 kg on average. In addition, a clear improvement in the glycaemic control was seen in the low-carbohydrate group after six months. Their average blood sugar level dropped from 58.5 to 53.7 mmol/mol (the unit for average blood glucose). This means that the intensity of the treatment for diabetes could also be reduced, and the amounts of insulin were lowered by 30%.

Despite the increased fat intake with a larger portion of saturated fatty acids, their lipoproteins did not get worse. Quite the contrary – the HDL, or ‘good’ cholesterol, content increased on the high fat diet.

No statistically certain improvements, either of the glycaemic controls or the lipoproteins, were seen in the low-fat group, despite the weight loss.

“You could ask yourself if it really is good to recommend a low-fat diet to patients with diabetes, if despite their weight loss they get neither better lipoproteins nor blood glucose levels,” Nyström says.

In the low-carbohydrate diet, 50% of the energy came from fat, 20% from carbohydrates, and 30% from protein. For the low-fat group the distribution was 30% from fat, 55-60% from carbohydrates, and 10-15% from protein, which corresponds to the diet recommended by the Swedish National Food Agency.

The participants were recruited from two primary health care centres and met for four group meetings during the first year of the study. All 61 participants remained in the study for the follow-up.

“In contrast to most other studies of this type, we lost no patients at all, which vouches for the good quality of our data,” Guldbrand says.

Flavonoid compound found in foods and supplements shown to prevent the formation of blood clots

Research findings offer a new direction for a therapeutic agent to prevent stroke, heart attack

BOSTON — A compound called rutin, commonly found in fruits and vegetables and sold over the counter as a dietary supplement, has been shown to inhibit the formation of blood clots in an animal model of thrombosis.

These new findings, led by investigators at Beth Israel Deaconess Medical Center (BIDMC) and published in today’s on-line issue of The Journal of Clinical Investigation (JCI), identify a novel strategy for preventing thrombosis, and help pave the way for clinical testing of this popular flavonoid as a therapy for the prevention and treatment of stroke and heart attack, as well as deep venous thrombosis (DVT) and pulmonary embolism.

“It’s not always fully appreciated that the majority of Americans will die as the result of a blood clot in either their heart or their brain,” says senior author Robert Flaumenhaft, MD, PhD, an investigator in the Division of Hemostasis andThrombosis at BIDMC and Associate Professor of Medicine at Harvard Medical School. “Approximately half of all morbidity and mortality in the United States can be attributed to heart attack or stroke.”

The study focused on protein disulfide isomerase (PDI) which is found in all cells. Investigators in BIDMC’s Division of Hemostasis and Thrombosis had previously shown that PDI is rapidly secreted from both platelets and endothelial cells during thrombosis, when a clot forms in a blood vessel, and that inhibition of PDI could block thrombosis in a mouse model.

“This was a transformative and unanticipated finding because it identified, for the first time, that PDI is secreted from cells in a live animal and is a potential target for preventing thrombosis,” says Flaumenhaft. However, because intracellular PDI is necessary for the proper synthesis of proteins, the scientists had to identify a specific compound that could block the thrombosis-causing extracellular PDI – without inhibiting the intracellular PDI.

They began by conducting a high-throughput screen of a wide array of compounds to identify PDI inhibitors. Among the more than 5,000 compounds that were screened, quercetin-3-rutinoside (rutin) emerged as the most potent agent. “Rutin was essentially the champion compound,” says Flaumenhaft.

A bioflavonoid that is naturally found in many fruits, vegetables and teas including onions, apples and citrus fruits, rutin is also sold as an herbal supplement, having received a special designation for safety from the U.S. Food and Drug Administration (FDA). Surprisingly, studies of the rutin molecule demonstrated that the same part of the molecule that provides rutin with its ability to inhibit PDI also prevents the compound from entering cells. “That finding explained how this compound can be both a potent inhibitor of PDI and a safe food supplement,” says Flaumenhaft. “Our next questions were, ‘Is this compound anti-thrombotic? Can it prevent blood clots?'”

The team went on to test rutin in a mouse model of thrombosis. Because they knew that humans would be taking rutin in pill form, they included studies in which the compound was administered orally and determined that it successfully retained its anti-thrombotic properties when it was metabolized following oral ingestion.

“Rutin proved to be the most potently anti-thrombotic compound that we ever tested in this model,” says Flaumenhaft. Of particular note, rutin was shown to inhibit both platelet accumulation and fibrin generation during thrombus formation. “Clots occur in both arteries and in veins,” explains Flaumenhaft. “Clots in arteries are platelet-rich, while those in veins are fibrin-rich. This discovery suggests that a single agent can treat and prevent both types of clots.”

Even with the use of existing anti-clotting therapies, such as aspirin, clopidogrel (Plavix) and warfarin (Coumadin), each year there are approximately 400,000 recurrent episodes among patients who previously experienced a stroke or heart attack, says Flaumenhaft.

“A safe and inexpensive drug that could reduce recurrent clots could help save thousands of lives,” he adds. “These pre-clinical trials provide proof-of-principle that PDI is an important therapeutic target for anti-thrombotic therapy, and because the FDA has already established that rutin is safe, we are poised to expeditiously test this idea in a clinical trial, without the time and expense required to establish the safety of a new drug.”

Soybeans soaking in warm water could become a new “green” source for production of a cancer-fighting substance now manufactured in a complicated and time-consuming industrial process, scientists are reporting in ACS’ Journal of Agricultural and Food Chemistry.

Hari B. Krishnan and colleagues explain that the substance, Bowman-Birk Protease Inhibitor (BBI), has shown promise for preventing certain forms of cancer in clinical trials. Those human tests resulted from evidence of BBI’s beneficial effects, including indications that BBI derived from the large amounts of soybeans in traditional Japanese diets might underpin low cancer mortality rates in Japan. However, the current method of extracting BBI from soybeans is time-consuming and involves harsh chemicals. The scientists set out to see if there might be a greener and more environmentally friendly way of obtaining BBI.

They found that soybean seeds incubated in water at 122 degrees Fahrenheit naturally release large amounts of BBI that can easily be harvested from the water. The protein appeared to be active, with tests showing that it stopped breast cancer cells from dividing in a laboratory dish. “The abundance of BBI in soybean seed exudates by incubating the seeds in warm water provides a simple and alternative method to isolate this low molecular weight protein,” the researchers said.

53 Million Americans Might Have Diabetes by 2025, According to a New Study in Population Health Management

New Rochelle, NY, May 15, 2012—The Diabetes 2025 Model for the U.S. projects a continuous and dramatic increase in the diabetes epidemic and makes it possible to estimate the potential effects of society-wide changes in lifestyle and healthcare delivery systems. Predictions for individual states and population subgroups are highlighted in an article published in Population Health Management, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The article is available free on the Population Health Management website.

“Diabetes is now a national security issue as it threatens all aspects of our nation’s well-being,” says Journal Editor-in-Chief David B. Nash, MD, MBA, Dean, Jefferson School of Population Health (Philadelphia, PA).

Based on their Diabetes 2025 Model, William Rowley, MD and Clement Bezold, PhD, Institute for Alternative Futures (Alexandria, VA), project that diabetes (mainly type 2 diabetes) will affect 53.1 million Americans by 2025, an increase of 64% from 2010. Their model can also be used to estimate the benefit of changes in lifestyle and specific interventions in reducing the burden of diabetes, according to the article “Creating Public Awareness: State 2025 Diabetes Forecasts.”

Sugar makes you stupid

UCLA study shows high-fructose diet sabotages learning, memory

Attention, college students cramming between midterms and finals: Binging on soda and sweets for as little as six weeks may make you stupid.

A new UCLA rat study is the first to show how a diet steadily high in fructose slows the brain, hampering memory and learning — and how omega-3 fatty acids can counteract the disruption. The peer-reviewed Journal of Physiology publishes the findings in its May 15 edition.

“Our findings illustrate that what you eat affects how you think,” said Fernando Gomez-Pinilla, a professor of neurosurgery at the David Geffen School of Medicine at UCLA and a professor of integrative biology and physiology in the UCLA College of Letters and Science. “Eating a high-fructose diet over the long term alters your brain’s ability to learn and remember information. But adding omega-3 fatty acids to your meals can help minimize the damage.”

While earlier research has revealed how fructose harms the body through its role in diabetes, obesity and fatty liver, this study is the first to uncover how the sweetener influences the brain.

The UCLA team zeroed in on high-fructose corn syrup, an inexpensive liquid six times sweeter than cane sugar, that is commonly added to processed foods, including soft drinks, condiments, applesauce and baby food. The average American consumes more than 40 pounds of high-fructose corn syrup per year, according to the U.S. Department of Agriculture.

“We’re not talking about naturally occurring fructose in fruits, which also contain important antioxidants,” explained Gomez-Pinilla, who is also a member of UCLA’s Brain Research Institute and Brain Injury Research Center. “We’re concerned about high-fructose corn syrup that is added to manufactured food products as a sweetener and preservative.”

Gomez-Pinilla and study co-author Rahul Agrawal, a UCLA visiting postdoctoral fellow from India, studied two groups of rats that each consumed a fructose solution as drinking water for six weeks. The second group also received omega-3 fatty acids in the form of flaxseed oil and docosahexaenoic acid (DHA), which protects against damage to the synapses — the chemical connections between brain cells that enable memory and learning.

“DHA is essential for synaptic function — brain cells’ ability to transmit signals to one another,” Gomez-Pinilla said. “This is the mechanism that makes learning and memory possible. Our bodies can’t produce enough DHA, so it must be supplemented through our diet.”

The animals were fed standard rat chow and trained on a maze twice daily for five days before starting the experimental diet. The UCLA team tested how well the rats were able to navigate the maze, which contained numerous holes but only one exit. The scientists placed visual landmarks in the maze to help the rats learn and remember the way.

Six weeks later, the researchers tested the rats’ ability to recall the route and escape the maze. What they saw surprised them.

“The second group of rats navigated the maze much faster than the rats that did not receive omega-3 fatty acids,” Gomez-Pinilla said. “The DHA-deprived animals were slower, and their brains showed a decline in synaptic activity. Their brain cells had trouble signaling each other, disrupting the rats’ ability to think clearly and recall the route they’d learned six weeks earlier.”

The DHA-deprived rats also developed signs of resistance to insulin, a hormone that controls blood sugar and regulates synaptic function in the brain. A closer look at the rats’ brain tissue suggested that insulin had lost much of its power to influence the brain cells.

He suspects that fructose is the culprit behind the DHA-deficient rats’ brain dysfunction. Eating too much fructose could block insulin’s ability to regulate how cells use and store sugar for the energy required for processing thoughts and emotions.

“Insulin is important in the body for controlling blood sugar, but it may play a different role in the brain, where insulin appears to disturb memory and learning,” he said. “Our study shows that a high-fructose diet harms the brain as well as the body. This is something new.”

Gomez-Pinilla, a native of Chile and an exercise enthusiast who practices what he preaches, advises people to keep fructose intake to a minimum and swap sugary desserts for fresh berries and Greek yogurt, which he keeps within arm’s reach in a small refrigerator in his office. An occasional bar of dark chocolate that hasn’t been processed with a lot of extra sweetener is fine too, he said.

Still planning to throw caution to the wind and indulge in a hot-fudge sundae? Then also eat foods rich in omega-3 fatty acids, like salmon, walnuts and flaxseeds, or take a daily DHA capsule. Gomez-Pinilla recommends one gram of DHA per day.

“Our findings suggest that consuming DHA regularly protects the brain against fructose’s harmful effects,” said Gomez-Pinilla. “It’s like saving money in the bank. You want to build a reserve for your brain to tap when it requires extra fuel to fight off future diseases.”

Ralph’s Note: 9 oz = 252 grams/ a day…Imagine swallowing 252 x 1000mg tablets ( 252,000 mg ) a day of a toxic substance every day for a year. There you the average have High fructose Corn Syrup in take a day of an American… The same ones that complain when you take ONE 1000mg capsule of Vitamin C.

Pregnant women in poor communities in Bangladesh who received multiple micronutrients, including iron and folic acid combined with early food supplementation, had substantially improved survival of their newborns, compared to women in a standard program that included usual food supplementation, according to a study in the May 16 issue of JAMA, a theme issue on Global Health.

“Maternal and child undernutrition is estimated to be the underlying cause of 3.5 million annual deaths and 35 percent of the total disease burden in children younger than 5 years. The potential long-term consequences of nutritional imbalance or insult in fetal or early life also include cognitive impairment and chronic diseases in adulthood. Effective child nutrition interventions are available to reduce stunting, prevent consequences of micronutrient deficiencies, and improve survival. The knowledge base is weaker regarding prenatal nutrition interventions of benefit for mother and offspring,” according to background information in the article. “The proportion of malnourished mothers and children remains high in many areas of the world, especially in South Asia, where more than one-quarter of newborns have a low weight.”

Lars Ake Persson, M.D., Ph.D., of Uppsala University, Uppsala, Sweden, and colleagues conducted a study (the MINIMat trial) to examine whether a prenatal multiple micronutrient supplementation (MMS), as well as an early invitation to a daily food supplementation, would increase maternal hemoglobin level at 30 weeks’ gestation, birth weight, and infant survival, and that a combination of these interventions (early invitation with MMS) would further improve these outcomes. The randomized trial, conducted in Matlab, Bangladesh, included 4,436 pregnant women who were recruited between November 2001 and October 2003, with follow-up until June 2009. One-third of the women were illiterate and one-fifth experienced occasional or constant deficit in their perceived income-expenditure status.

Participants were randomized into 6 groups; a double-masked supplementation with capsules of 30 mg of iron and 400 μg of folic acid, 60 mg of iron and 400 μg of folic acid, or MMS containing a daily allowance of 15 micronutrients, including 30 mg of iron and 400 μg of folic acid, was combined with food supplementation randomized to either early invitation (9 weeks’ gestation) or usual invitation (20 weeks’ gestation).

There were 3,625 live births out of 4,436 pregnancies. The average birth weight among 3,267 single-birth infants was 2,694 grams (5.9 lbs.). Overall, 31 percent of newborns weighed less than 2,500 g (5.5 lbs.). There was no significant difference in birth weight among treatment groups, and no main-effect differences between food groups or among micronutrient groups. The researchers found that infants in the early invitation with MMS group had a lower risk of death, with a mortality rate of 16.8 per 1,000 live births vs. 44.1 per 1,000 live births for usual invitation with 60 mg of iron and 400 μg of folic acid. The early invitation with MMS group had an under 5-year mortality rate of 18 per 1,000 live births (54 per 1,000 live births for usual invitation with 60 mg of iron and 400 μg of folic acid). Usual care invitation with MMS had the highest infant mortality rate (47.1 per 1,000 live births).

Adjusted maternal hemoglobin level at 30 weeks’ gestation was 115.0 g/L, with no significant differences among micronutrient groups. Women in the early invitation group had a small (0.9 g/L) but statistically significant lower hemoglobin level concentration than those in the usual invitation group.

“Scientists and policymakers have recommended replacing the current iron-folic acid supplements with MMS in the package of health and nutrition interventions delivered to pregnant women to improve size at birth and child growth and development. Other studies have questioned this view based on the limited size of the effect on birth weight and the absence of positive effect on fetal and neonatal survival. The MINIMat trial provides evidence that mortality of the offspring was reduced if multiple micronutrients were combined with a balanced protein-energy supplementation that began early in pregnancy,” the researchers conclude.

(JAMA. 2012;307[19]:2050-2059. Available pre-embargo to the media at www.jamamedia.org)

Ralph’s Note – Vitamin and Nutrients had 16.8 deaths…Compared to food only 44 deaths per 1000.

McLean Hospital study finds herbal extract may curb binge drinking

Belmont, MA – An extract of the Chinese herb kudzu dramatically reduces drinking and may be useful in the treatment of alcoholism and curbing binge drinking, according to a new study by McLean Hospital and Harvard Medical School researchers.

“Our study is further evidence that components found in kudzu root can reduce alcohol consumption and do so without adverse side effects,” said David Penetar, PhD, of the Behavioral Psychopharmacology Research Laboratory at McLean Hospital, and the lead author of the study. “Further research is needed, but this botanical medication may lead to additional methods to treat alcohol abuse and dependence.”

In the study, published in the current issue of Drug and Alcohol Dependence, researchers in the Behavioral Psychopharmacology Research Laboratory at McLean Hospital looked at one of the major components of the kudzu root—the isoflavone puerarin—to determine whether it would reduce alcohol consumption in a laboratory simulation of an afternoon drinking session.

According to Penetar, puerarin was selected over other kudzu root components because its safety and efficacy have already been established in humans, particularly in China where it is approved for intravenous injection to treat coronary heart disease, myocardial infarction and angina. Puerarin is also less potent than other parts of the kudzu plant, so it has few side effects and has none of the estrogenic activity found in other components, making it safe for women.

In the study, Penetar and his colleagues looked at 10 men and women, all in their 20s and all reporting regularly consuming alcohol weekly. A laboratory at McLean Hospital was set up as an apartment, with TV, DVD player, reclining chair and other amenities. The unit was also stocked with a refrigerator full of each subject’s favorite beer and other non-alcoholic beverages.

In an initial 90-minute session in the “apartment,” each subject was allowed to consume as many beers as he or she wanted—up to a maximum of six. After the session, each was given either puerarin or a placebo and told to take it daily for a week. Then, each returned to do the experiment again. Two weeks later, the subjects returned for a third session to see if they had returned to their baseline drinking levels. After that, each subject was given the pill he or she didn’t get the first time and told to take it for a week. Each then returned for a fourth and final drinking session.

The study showed that subjects taking puerarin drank significantly fewer beers—dropping from 3.5 beers on average to 2.4.

“This was a simulation of a binge drinking opportunity and not only did we see the subjects drinking less, we noted that their rate of consumption decreased, meaning they drank slower and took more sips to finish a beer,” explained Penetar. “While we do not suggest that puerarin will stop drinking all together, it is promising that it appears to slow the pace and the overall amount consumed.”

The Behavioral Psychopharmacology Research Laboratory at McLean Hospital has been involved in a series of research projects for more than 10 years, looking at the ability of extracts of the kudzu root and its components to reduce excessive drinking with very encouraging results.

These reports are done with the appreciation of all the Doctors, Scientist, and other

Medical Researchers who sacrificed their time and effort. In order to give people the

ability to empower themselves. Without the base aspirations for fame, or fortune. Just honorable people, doing honorable things.